chr10-68231992-T-G

Variant names:

• chr10-68231992-T-G
• rs61854782
• NM_145178.4:c.-315A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145178.4(ATOH7):​c.-315A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 171,484 control chromosomes in the GnomAD database, including 2,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2015 hom., cov: 33)
  • Exomes 𝑓: 0.19 (333 hom.)
• Consequence: ATOH7 NM_145178.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0240
• Publications: 15 publications found

Genes affected

ATOH7 (HGNC:13907): (atonal bHLH transcription factor 7) This intronless gene encodes a member of the basic helix-loop-helix family of transcription factors, with similarity to Drosophila atonal gene that controls photoreceptor development. Studies in mice suggest that this gene plays a central role in retinal ganglion cell and optic nerve formation. Mutations in this gene are associated with nonsyndromic congenital retinal nonattachment. [provided by RefSeq, Dec 2011]

ATOH7 Gene-Disease associations (from GenCC):

• persistent hyperplastic primary vitreous, autosomal recessive

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• persistent hyperplastic primary vitreous

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• anterior segment dysgenesis 7

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 10-68231992-T-G is Benign according to our data. Variant chr10-68231992-T-G is described in ClinVar as Benign. ClinVar VariationId is 1266780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATOH7	NM_145178.4	c.-315A>C		5_prime_UTR_variant	Exon 1 of 1	ENST00000373673.5	NP_660161.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATOH7	ENST00000373673.5	c.-315A>C		5_prime_UTR_variant	Exon 1 of 1	6	NM_145178.4	ENSP00000362777.3

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21304 AN: 152112 Hom.: 2012 Cov.: 33

Gnomad AFR AF: 0.0323

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.194 AC: 3727 AN: 19254 Hom.: 333 Cov.: 0 AF XY: 0.198 AC XY: 1849 AN XY: 9362

African (AFR) AF: 0.0185 AC: 3 AN: 162

American (AMR) AF: 0.365 AC: 35 AN: 96

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 61 AN: 180

East Asian (EAS) AF: 0.144 AC: 54 AN: 374

South Asian (SAS) AF: 0.132 AC: 5 AN: 38

European-Finnish (FIN) AF: 0.197 AC: 2967 AN: 15068

Middle Eastern (MID) AF: 0.111 AC: 2 AN: 18

European-Non Finnish (NFE) AF: 0.183 AC: 543 AN: 2964

Other (OTH) AF: 0.161 AC: 57 AN: 354

GnomAD4 genome AF: 0.140 AC: 21318 AN: 152230 Hom.: 2015 Cov.: 33 AF XY: 0.144 AC XY: 10731 AN XY: 74432

African (AFR) AF: 0.0322 AC: 1337 AN: 41578

American (AMR) AF: 0.215 AC: 3286 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3470

East Asian (EAS) AF: 0.139 AC: 722 AN: 5176

South Asian (SAS) AF: 0.191 AC: 923 AN: 4828

European-Finnish (FIN) AF: 0.198 AC: 2094 AN: 10588

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.168 AC: 11413 AN: 67990

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.147 Hom.: 1038

Bravo AF: 0.139

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		0.024
PromoterAI		-0.057	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61854782; hg19: chr10-69991749;